Bojic Suzana, Kotur-Stevuljevic Jelena, Kalezic Nevena, Stevanovic Predrag, Jelic-Ivanovic Zorana, Bilanovic Dragoljub, Memon Lidija, Damnjanovic Mladen, Kalaba Zdravko, Simic-Ogrizovic Sanja
Department of Anaesthesiology, Resuscitation and Intensive Care, Clinical Hospital Center Bezanijska Kosa.
Tohoku J Exp Med. 2015 Oct;237(2):103-9. doi: 10.1620/tjem.237.103.
Sepsis-associated acute kidney injury (SA-AKI) severely impacts morbidity and mortality in surgical patients with sepsis. Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) have an important role in pathophysiology of sepsis but they have been unexplored in SA-AKI. We aimed to investigate the role of MMP-9 and TIMP-1 in septic surgical patients with SA-AKI and to evaluate them as diagnostic biomarkers of SA-AKI. This prospective observational study compared 53 major abdominal surgery patients with sepsis divided into SA-AKI (n = 37) and non-SA-AKI (n =16) group to 50 controls without sepsis matched by age, gender, comorbidities and type of surgery. Blood and urine samples from septic patients were collected on admission to ICU and 24, 48, 72 and 96 h later and once from the controls. The levels of MMP-9, TIMP-1, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1, urea and creatinine were measured. MMP-9/TIMP-1 ratio and disease severity scores, such as Sequential Organ Failure Assessment (SOFA), were calculated. Septic patients with SA-AKI had higher serum TIMP-1 levels and lower serum MMP-9 levels and lower MMP-9/TIMP ratio, compared to septic patients without SA-AKI and controls. The levels of these biomarkers did not change significantly over time. MMP-9, TIMP-1 and MMP-9/TIMP-1 ratio correlated with urea, creatinine, NGAL, and SOFA scores. Moreover, using the area under ROC curve, we showed that TIMP-1 and MMP-9/TIMP-1 ratio, but not MMP-9, were good diagnostic biomarkers of SA-AKI. We report for the first time the potential diagnostic value of TIMP-1 and MMP-9/TIMP-1 ratio in SA-AKI.
脓毒症相关急性肾损伤（SA-AKI）严重影响脓毒症手术患者的发病率和死亡率。基质金属蛋白酶-9（MMP-9）和基质金属蛋白酶组织抑制剂-1（TIMP-1）在脓毒症的病理生理学中起重要作用，但它们在SA-AKI中的作用尚未得到研究。我们旨在研究MMP-9和TIMP-1在伴有SA-AKI的脓毒症手术患者中的作用，并评估它们作为SA-AKI诊断生物标志物的价值。这项前瞻性观察性研究将53例患有脓毒症的腹部大手术患者分为SA-AKI组（n = 37）和非SA-AKI组（n = 16），并与50例年龄、性别、合并症和手术类型相匹配的无脓毒症对照组进行比较。脓毒症患者在入住重症监护病房时、之后24、48、72和96小时采集血液和尿液样本，对照组仅采集一次。检测MMP-9、TIMP-1、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、肾损伤分子-1、尿素和肌酐的水平。计算MMP-9/TIMP-1比值以及疾病严重程度评分，如序贯器官衰竭评估（SOFA）评分。与无SA-AKI的脓毒症患者和对照组相比，伴有SA-AKI的脓毒症患者血清TIMP-1水平较高，血清MMP-9水平较低，MMP-9/TIMP比值也较低。这些生物标志物的水平随时间没有显著变化。MMP-9、TIMP-1和MMP-9/TIMP-1比值与尿素、肌酐、NGAL和SOFA评分相关。此外，通过ROC曲线下面积分析，我们发现TIMP-1和MMP-9/TIMP-1比值而非MMP-9是SA-AKI的良好诊断生物标志物。我们首次报道了TIMP-1和MMP-9/TIMP-1比值在SA-AKI中的潜在诊断价值。
